Safety of the weight-adjusted dosing regimen of tenecteplase in the ASSENT-Trial.

The results of the ASsessment of Safety and Efficacy of a New Thrombolytic agent (ASSENT-2) trial revealed that tenecteplase (TNK) is equivalent to tissue plasminogen activator (t-PA) for treating myocardial infarction. Because careful consideration of safety is important with all agents, including the newer bolus therapies, and across a range of doses, this study evaluated the safety of TNK compared with t-PA across a range of weight and dose categories. The 5 doses of TNK ranged from 30 to 50 mg and were adjusted for estimated weight. Rates of death and intracranial hemorrhage were determined among patients receiving TNK and t-PA in ASSENT-2, stratified by categories of estimated weight corresponding to each TNK dose. Respective rates of death with TNK versus t-PA were not significantly different in any estimated weight category: <60 kg (12.54% vs 11.46%), 60 to 69 kg (8.22% vs. 8.97%), 70 to 79 kg (5.57% vs 5.48%), 80 to 89 kg (4.66% vs 5.36%), and > or =90 kg (4.91% vs. 3.96%, all p > or =0.26). Respective rates of intracranial hemorrhage were also not significantly different: <60 kg (2.20% vs. 2.29%), 60 to 69 kg (0.97% vs. 1.33%), 70 to 79 kg (1.15% vs. 1.10%), 80 to 89 kg (0.73% vs 0.49%), and > or =90 kg (0.47% vs 0.47%, all p > or =0.33). Adjustment for small baseline differences in this randomized sample did not change the results. Thus, across the range of estimated weight categories corresponding to each TNK dose, TNK is as safe and effective as t-PA.

Hormone therapy and in-hospital survival after myocardial infarction in postmenopausal women.

BACKGROUND: Although postmenopausal hormone therapy (HRT) commonly is used in hope of preventing coronary heart disease, the effect of HRT on case fatality of myocardial infarction has never been studied. We evaluated HRT as a predictor of survival after MI in postmenopausal women. METHODS AND RESULTS: The present study was performed with 114 724 women of age >/=55 years with confirmed myocardial infarction who presented between April 1998 and January 2000 to 1 of 1674 hospitals participating in the National Registry of Myocardial Infarction-3. Presenting characteristics, treatment, and clinical outcome data were obtained by chart review. At time of hospitalization, 7353 (6.4%) women reported current use of HRT, defined as use of estrogen, progestin, or estrogen/progestin for reasons other than contraception. Unadjusted mortality was 7.4% in users of HRT and 16.2% in nonusers (odds ratio 0.41, 95% confidence interval 0.36 to 0.43). After adjustments were made for prior medical history, clinical characteristics, treatments received in-hospital, and likelihood of receiving HRT, HRT remained associated with an improved rate of survival (odds ratio 0.65, 95% confidence interval 0.59 to 0.72). Significant association of HRT with decreased mortality after myocardial infarction was observed in all age strata. CONCLUSIONS: Postmenopausal HRT appears to be associated with reduced mortality after myocardial infarction. This finding could be caused by therapeutic effect of HRT, selection and adherence bias, or some combination of both.

Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women.

OBJECTIVES: We examined the association of hormone therapy (HRT) with hemorrhagic and ischemic stroke among postmenopausal women with acute myocardial infarction (AMI). BACKGROUND: Hemorrhagic and ischemic strokes are common complications of AMI, and women are at increased risk for hemorrhagic stroke after thrombolytic therapy. This risk may be related to female hormones. METHODS: Using data from the National Registry of Myocardial Infarction-3, we studied 114,724 women age 55 years or older admitted to the hospital for AMI, of whom 7,353 reported HRT use on admission. We determined rates of in-hospital hemorrhagic and ischemic stroke stratified by HRT use and estimated the independent association of HRT with each stroke type using multivariable logistic regression. RESULTS: The HRT users were younger than non-users, had fewer risk factors for stroke including diabetes and prior stroke, and received more pharmacologic and invasive therapy including cardiac catheterization. A total of 2,152 (1.9%) in-hospital strokes occurred, with 442 (0.4%) hemorrhagic, 1,017 (0.9%) ischemic and 693 (0.6%) unspecified. Among HRT users and non-users, the rates of hemorrhagic stroke (0.40% vs. 0.42%, p = 1.00) and ischemic stroke (0.80% vs. 0.96%, p = 0.11) were similar. Among 13,328 women who received thrombolytic therapy, the rate of hemorrhagic stroke was not significantly different for users and non-users (1.6% vs. 2.1%, p = 0.22). After adjustment for baseline and treatment differences, HRT was not associated with hemorrhagic (odds ratio [OR], 0.88; 95% confidence intervals [CI], 0.58 to 1.35) or ischemic stroke (OR, 0.89; CI, 0.66 to 1.18). CONCLUSIONS: Acute myocardial infarction is a high-risk setting for stroke among postmenopausal women, but HRT does not appear to modify that risk. Clinicians should not alter their approach to thrombolytic therapy based on HRT use.

Use of reperfusion therapies in elderly patients with acute myocardial infarction.

Almost one-third of patients with acute myocardial infarction (AMI) are aged >75 years, and this proportion is expected to increase as the population ages. Mortality and complication rates are particularly high in the elderly, yet reperfusion therapies, including thrombolysis and primary percutaneous transluminal coronary angioplasty (PTCA), are under-utilised among eligible patients. There is a concern, whether real or perceived, that the risks of such therapies may outweigh the potential benefits. Presently, there are no randomised clinical trials of thrombolytic therapy in the elderly that definitively assess its efficacy in patients aged >75 years. In the meta-analysis of randomised trials by the Fibrinolytic Therapy Trialists, thrombolysis was associated with a mortality reduction among patients aged >75 years, though this reduction did not meet formal statistical significance. Because the point estimates for mortality reduction were in the direction that favoured use of thrombolytic therapy, the American Heart Association/American College of Cardiology AMI guidelines recommend thrombolysis as a Class 2a therapy in this age group. Observational studies using data from the Cooperative Cardiovascular Project database and the National Registry of Myocardial Infarction have recently cast some doubt on the benefit of thrombolysis among the elderly, but definitive answers from a randomised trial are still lacking. Meanwhile, primary PTCA, which has been compared to thrombolysis in both trial and observational settings, appears to offer the mortality benefit of reperfusion with lower stroke rates. Since primary PTCA is not widely available, efforts must be made to maximise available therapies in the elderly. Early diagnosis is essential, as is prompt reperfusion among eligible patients, since delay is so strongly associated with mortality with both thrombolysis and PTCA. Finally, newer, more fibrin-specific thrombolytics may decrease the bleeding risk associated with thrombolytic therapy.

The use of intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction: data from the National Registry of Myocardial Infarction 2.

BACKGROUND: Cardiogenic shock complicating acute myocardial infarction (AMI) remains the leading cause of death in patients hospitalized with AMI. Although several studies have demonstrated the importance of establishing and maintaining a patent infarct-related artery, it remains unclear as to whether intra-aortic balloon counterpulsation (IABP) provides incremental benefit to reperfusion therapy. The purpose of this study was to determine whether IABP use is associated with lower in-hospital mortality rates in patients with AMI complicated by cardiogenic shock in a large AMI registry. METHODS: We evaluated patients participating in the National Registry of Myocardial Infarction 2 who had cardiogenic shock at initial examination or in whom cardiogenic shock developed during hospitalization (n = 23,180). RESULTS: The mean age of patients in the study was 72 years, 54% were men, and the majority were white. The overall mortality rate in all patients who had cardiogenic shock or in whom cardiogenic shock developed was 70%. IABP was used in 7268 (31%) patients. IABP use was associated with a significant reduction in mortality rates in patients who received thrombolytic therapy (67% vs 49%) but was not associated with any benefit in patients treated with primary angioplasty (45% vs 47%). In a multivariate model, the use of IABP in conjunction with thrombolytic therapy decreased the odds of death by 18% (odds ratio, 0.82; 95% confidence interval, 0.72 to 0.93). CONCLUSIONS: Patients with AMI complicated by cardiogenic shock may have substantial benefit from IABP when used in combination with thrombolytic therapy.

Death or nonfatal stroke in patients with acute myocardial infarction treated with tissue plasminogen activator. Participants in the National Registry of Myocardial Infarction 2.

In a retrospective cohort of patients treated in community hospitals, tissue plasminogen activator (t-PA) was associated with decreased odds of in-hospital death or nonfatal stroke. However, the relative benefit was less evident in older patients and women, and some older subgroups did not benefit from treatment.